No abstract

There is a high prevalence of sleep disorder-related symptoms in pregnant women. Our data may provide a baseline for prevention and treatment of sleep disturbances in pregnant women.

Osteoarthritis (OA) is a complex condition that involves both apoptosis and senescence and currently cannot be cured. Fibroblast growth factor 21 (FGF21), known for its role as a potent regulator of glucose and energy metabolism, protects from various diseases, possibly by mediating autophagy. In the present study, the role of FGF21 in the progression of OA was investigated in both in vitro and in vivo experiments. In vitro, the results revealed that FGF21 administration alleviated apoptosis, senescence, and extracellular matrix (ECM) catabolism of the chondrocytes induced by tert-butyl hydroperoxide (TBHP) by mediating autophagy flux. Furthermore, CQ, an autophagy flux inhibitor, could reverse the protective effect of FGF21. It was observed that the FGF21-induced autophagy flux enhancement was mediated by the nuclear translocation of TFEB, which occurs due to the activation of the SIRT1-mTOR signaling pathway. The in vivo experiments demonstrated that FGF21 treatment could reduce OA in the DMM model. Taken together, these findings suggest that FGF21 protects chondrocytes from apoptosis, senescence, and ECM catabolism via autophagy flux upregulation and also reduces OA development in vivo, demonstrating its potential as a therapeutic agent in OA.

Epileptic encephalopathies (EE) are a group of severe childhood epilepsy disorders characterized by intractable seizures, cognitive impairment and neurological deficits. Recent whole-exome sequencing (WES) studies have implicated significant contribution of de novo mutations to EE. In this study, we utilized WES for identifying causal de novo mutations in 4 parent-offspring trios affected by West syndrome. As a result, we found two deleterious de novo mutations in DYNC1H1 and RTP1 in two trios. Expression profile analysis showed that DYNC1H1 and RTP1 are expressed in almost all brain regions and developmental stages. Interestingly, co-expression and genetic interaction network analyses suggested that DYNC1H1 and RTP1 are tightly associated with known epilepsy genes. Furthermore, we observed that the de novo mutations of DYNC1H1 were identified in several different neuropsychiatric disorders including EE, autism spectrum disorders and intellectual disabilities by previous studies, and these mutations primarily occurred in the functional domain of the protein. Taken together, these results demonstrate DYNC1H1 as a strong candidate and RTP1 as a potential candidate on the onset of EE. In addition, this work also proves WES as a powerful tool for the molecular genetic dissection of children affected by sporadic EE.